In recent years, much attention has been given to site-specific delivery of drugs within a patient. Although various drugs have been developed for treatment of a wide variety of ailments and diseases of the body, in many instances, such drugs cannot be effectively administered systemically without risk of detrimental side effects. Site-specific drug delivery focuses on delivering the drugs locally, i.e., to the area of the body requiring treatment. One benefit of the local release of bioactive agents is the avoidance of toxic concentrations of drugs that are at times necessary, when given systemically, to achieve therapeutic concentrations at the site where they are required.
Site-specific drug delivery can be accomplished by injection and/or implantation of an article or device that releases the drug to the treatment site. Injection of drugs can have limitations, for example, by requiring multiple administrations, increasing risk of complications (such as infection), and patient discomfort. Implantation of an article or device that delivers drug to the treatment site has therefore gained much interest in recent years.
Further, site-specific drug delivery has been enhanced by technologies that allow controlled release of one or more drugs from an implanted article. Controlled release can relate to the duration of time drug is released from the device or article, and/or the rate at which the drug is released.
Several challenges confront the use of medical devices or articles that release bioactive agents into a patient's body. For example, treatment may require release of the bioactive agent(s) over an extended period of time (for example, weeks, months, or even years), and it can be difficult to sustain the desired release rate of the bioactive agent(s) over such long periods of time.
While advances in site-specific implantable drug delivery systems have been made, many systems do not release drug in a desired manner following implantation in a patient. For example, in many systems the majority of the drug present in the article is released from the device in an initial burst, resulting in premature depletion of the drug. Following this depletion, the drug may be delivered to the subject in sub-optimal amounts.
In other systems, such as those based on polylactide-type biodegradable polymers, the majority of drug may be released at later points during the administration period due to bulk erosion of the drug containing biodegradable matrices.
If drug is prematurely released from the implant, or not released until later, the duration of treatment or the rate of release may not be as long as desired. This can cause the implant to be therapeutically less effective.
In addition, many drug delivery systems may demonstrate a great variation in the rate of drug release over the period of implantation. In these cases, an optimal rate of drug release may be seen only during a very small window over the period of implantation.
Other concerns regarding medical implants relate to biocompatibility. If materials that are used to prepare the implant promote an adverse tissue response in the body, the effectiveness of the implant can be reduced.
For example, as an alternative to non-biodegradable systems, synthetic biodegradable polymers, such as polyglycolide-type molecules, have been used for the construction of implantable medical devices and for delivery of bioactive agents. These types of biodegradable materials have the potential to degrade into products that cause unwanted side effects in the body by virtue of their presence or concentration in vivo. These unwanted side effects can include immune reactions, toxic buildup of the degradation products in the body, or the initiation or provocation of other adverse effects on cells or tissue in the body.